Anterior cruciate ligament (ACL) reconstructive surgeries are often successful at improving joint stability, but patients have a highly elevated rik for developing early onset osteoarthritis (OA). It is not well understood why OA develops in these patients, or how one can best plan a treatment strategy to mitigate the risk for OA. This is a very challenging question to answer empirically, since prospective studies require large subject numbers and many years to decipher. Current computational models in biomechanics are ill-suited to solve this problem because they decouple behavior that occurs at the macro (whole body) and micro (tissue mechanics) scales. Hence, a new multi-scale computational construct is being formulated to examine the inherent coupling that exists between musculoskeletal dynamics and soft tissue mechanics during gait. This construct is used to gain insights into the key surgical factors that can affect cartilage contact stresses after ACL reconstruction, which are believed to predicate osteoarthritic changes to the joint. The three aims of the study are to: 1) Assess effects of ACL graft stiffness, pre-tension and tunnel architecture on intra-operative assessments of knee laxity, 2) Investigate the coupled influence of surgical factors and muscle forces on in vivo knee mechanics as measured using dynamic MRI, 3) Investigate the multi-scale biomechanical behavior of reconstructed knees during human locomotion. These aims are used to test the hypothesis that articular cartilage contact stress magnitudes and location vary significantly with active muscle loading, and are also highly sensitive to the position and orientation of the tunnels used to reconstruct the ACL. The results of these studies are important for informing clinical approaches that can best mitigate the risk fo OA following ligament injury and surgical repair.